Concentrations of endometrial protein PP 14 and CA-125 in uterine flushings performed in natural and stimulated cycles

BACKGROUND: Impaired implantation in assisted reproduction cycles with high serum estradiol (E(2)) concentrations may be attributed to abnormal endometrial development. This study compared concentrations of endometrial proteins in uterine flushings of infertile patients between natural and stimulated cycles. METHODS: Patients received a standard regimen of ovarian stimulation. Seven days after the LH surge in natural cycles or the hCG injection in stimulated cycles, uterine flushings were performed by slowly injecting and aspirating normal saline through a paediatric Foley catheter. Natural cycles were considered as group A whereas stimulated cycles with serum E(2) <20 000 pmol/l and serum E(2) >20 000 pmol/l were classified as groups B and C respectively. PP 14 and CA-125 in uterine flushings were measured and expressed per total protein content. RESULTS: Concentrations of the total protein, PP 14 and CA-125 in the uterine flushings were similar among the three groups. PP 14 per total protein in the uterine flushings was significantly correlated with serum E(2) on the day of hCG (r = 0.459; P = 0.009) in natural cycles only but not in stimulated cycles. CONCLUSION: There was no significant difference between natural and stimulated cycles in concentrations of PP 14 and CA-125 in uterine flushings performed in the mid-luteal phase.     

Influence of wet surfaces and fall height on pediatric injury risk in feet-first freefalls as predicted using a test dummy

INTRODUCTION: Falls are a major cause of morbidity and mortality in children, but are also reported falsely in child abuse. Therefore, it is of interest to understand those factors which may lead to a higher likelihood of injury in a feet-first freefall. METHODS: We used laboratory freefall experiments and a 3-year-old Hybrid III anthropomorphic test dummy (ATD) to assess head and femur injury risk. Wet and dry linoleum impact surfaces were used from three fall heights: 22, 35 and 47 in. RESULTS: For a given fall height, dry surfaces were associated with higher head injury criteria (HIC) values than wet surfaces. Changes in fall height 22-47 in. did not significantly affect HIC values for falls onto either surface. Generally, compressive and bending femur loading increased significantly for wet as compared to dry linoleum. CONCLUSIONS: In simulated feet first freefall experiments up to 47 in. using a 3-year-old test dummy, a low risk of contact type head injury and femur fracture was found. However, both fall height and surface conditions influenced femur loading and head injury measures. Future efforts should explore the risk of head injury associated with angular acceleration in freefalls.     

Mariner is defective in myosin VIIA: a zebrafish model for human hereditary deafness

The zebrafish (Danio rerio) possesses two mechanosensory organs believed to be homologous to each other: the inner ear, which is responsible for the senses of audition and equilibrium, and the lateral line organ, which is involved in the detection of water movements. Eight zebrafish circler or auditory/vestibular mutants appear to have defects specific to sensory hair cell function. The circler genes may therefore encode components of the mechanotransduction apparatus and/or be the orthologous counterparts of the genes underlying human hereditary deafness. In this report, we show that the phenotype of the circler mutant, mariner, is due to mutations in the gene encoding Myosin VIIA, an unconventional myosin which is expressed in sensory hair cells and is responsible for various types of hearing disorder in humans, namely Usher 1B syndrome, DFNB2 and DFNA11. Our analysis of the fine structure of hair bundles in the mariner mutants suggests that a missense mutation within the C-terminal FERM domain of the tail of Myosin VIIA has the potential to dissociate the two different functions of the protein in hair bundle integrity and apical endocytosis. Notably, mariner sensory hair cells display morphological and functional defects that are similar to those present in mouse shaker-1 hair cells which are defective in Myosin VIIA. Thus, this study demonstrates the striking conservation of the function of Myosin VIIA throughout vertebrate evolution and establishes mariner as the first fish model for human hereditary deafness.     

A Randomized Clinical Trial of Topical Cysteamine Disulfide (Cystamine) versus Free Thiol (Cysteamine) in the Treatment of Corneal Cystine Crystals in Cystinosis

In nephropathic cystinosis, corneal cystine crystals cause severe photophobia and corneal erosions. Topical cysteamine dissolves these crystals, but cannot be marketed because it rapidly oxidizes to the disulfide form, cystamine, at room temperature. Since cystamine itself could be used commercially, we compared the efficacy of cystamine and cysteamine with respect to cystine crystal dissolution in a randomized, double-masked clinical trial. One eye each of 14 patients with cystinosis was randomized to either cystamine or cysteamine, 0.5%, with 0.01% benzalkonium chloride; the companion eye was treated with the alternate preparation. Corneal crystals were photographed and a density score was assigned to each slide based on 13 standard slides. After 8–20 months, 6 patients showed significant reduction of the corneal crystal score in only one eye. In each case, the improved eye was the cysteamine-treated eye. Theoretically, cysteamine should dissolve both intracellular and extracellular crystals, whereas cystamine should dissolve only intracellular crystals because it must first be reduced to the free thiol by the cytoplasmic-reducing environment. Hence, the lack of efficacy of the disulfide cystamine suggests that some corneal cystine crystals in cystinosis patients are extracellular, and that another form of stable, topical cysteamine must be developed for cystinosis patients.     

Genetic counseling dilemmas: Down syndrome,paternal age,and recurrence risk after remarriage

The recent demonstration that about 20–30% of cases of Down syndrome are of paternal origin has again raised interest in the question of the possible contribution of paternal age independent of maternal age to a couple's risk of a Down syndrome live birth. In this paper the nature of the available evidence is critically reviewed, interpretations reconciling differences between studies that reached opposite conclusions are presented, and an approach to genetic counseling in the face of such apparent differences in the literature is discussed. It is not likely that data from ad hoc studies of parental origin of the extra chromosome will be sufficient to judge the existence or magnitude of paternal age-specific risk, and reliance must be made on statistical studies that searched for paternal age effects while controlling for maternal age. The literature is consistent with an apparent doubling of risk for paternal age 55 and over, but no effect at younger paternal ages. With regard to remarriage, it is suggested that if members of a couple with a 47, +21 child remarry it be assumed that the excess risk “travels” to that new couple which includes the parent in whom non-disjunction occurred in the previous marriage. If parental origin is not known, it is suggested that the risk be calculated on the assumption of a 20–30% likelihood that it was of paternal origin and a 70–80% likelihood that it was of maternal origin, and that the excess empiric risks be apportioned accordingly in the new marriages.     

Cytogenetic findings in a parent of a patient with Fanconi''s anemia

We have studied a patient with clinically established Fanconi type anemia whose peripheral blood leukocyte culture and bone marrow showed a normal male karyotype, with no morphological alterations. The skin fibroblasts in cultures derived from his father, however, revealed a mosaic pattern, 47 , XY F+/46, XY. The findings of a trisomic cell line in a parent of a patient with Fanconi's anemia has been reported only once before.     

Endometrial and subendometrial blood flow measured during early luteal phase by three-dimensional power Doppler ultrasound in excessive ovarian responders

BACKGROUND: Impaired implantation in assisted reproduction cycles with high serum estradiol (E(2)) concentrations may be related to suboptimal endometrial perfusion. Endometrial and subendometrial blood flow were compared between excessive responders (serum E(2) on the day of HCG >20 000 pmol/l) and moderate responders (E(2) < or =20 000 pmol/l). METHODS: Three-dimensional (3D) ultrasound examination with power Doppler was performed 2, 4 and 7 days after HCG in 32 patients who did not have embryo transfer in order to measure endometrial thickness, pulsatility index (PI)/resistance index (RI) of uterine vessels, and endometrial volume, vascularization index (VI)/flow index (FI)/vascularization flow index (VFI) of endometrial and subendometrial regions. RESULTS: Excessive responders tended to have lower endometrial and subendometrial VI/VFI on HCG +2 and more absent endometrial/subendometrial blood flow. They had significantly higher endometrial FI and subendometrial VFI than moderate responders on HCG +7. Only in the excessive responder group, uterine PI/RI declined significantly from HCG +2 to HCG +7 and endometrial VI/VFI increased significantly from HCG +4 to HCG +7. CONCLUSION: Changes in uterine Doppler flow indices, and endometrial and subendometrial 3D power Doppler flow indices during the early luteal phase were significantly different between moderate and excessive responders.     

Drosophila dSAP18 is a nuclear protein that associates with chromosomes and the nuclear matrix, and interacts with pinin, a protein factor involved in RNA splicing

SAP18 is a highly conserved protein that was proposed to be involved in multiple cellular processes from autophagy to gene regulation and mRNA processing. In this paper we show that, in Drosophila, dSAP18 is a predominantly nuclear protein that associates to both chromosomes and the nuclear matrix. dSAP18 becomes nuclear early during development, at the onset of cellularization, and remains so all through embryo development. dSAP18 is also nuclear in salivary glands, ovaries and cultured S2 cells. Here we also show that dSAP18 forms a complex with the Drosophila homolog of pinin (dPnn), a protein factor involved in mRNA splicing. dSAP18-dPnn interaction was confirmed in vivo, through co-immunoprecipitation experiments, as well as in vitro, through GST pull-down assays. These results are discussed in the context of the possible functions played by SAP18.